The regulation of protein synthesis at the level of translation initiation plays a key role in the control of cell growth, proliferation, and apoptosis. The interaction between the initiation factors eIF4E and eIF4G is a major component of this process. eIF4E binds the 7-methylguanosine cap structure found at the 5′ ends of most messenger RNAs. Its binding partner eIF4G, a scaffold protein, provides a docking site for other initiation factors, including the RNA helicase eIF4A. Collectively, eIF4E, eIF4G, and eIF4A forms a ternary complex referred to as eIF4F. Once assembled, this complex recruits the 40S ribosomal subunit to the 5′ end of the mRNA molecule as a result of the interaction of eIF3 with eIF4G, followed by scanning of the 40S subunit to the initiation codon where it joins with the 60S subunit. This process is facilitated by eIF4A, with the requirement for its helicase activity being directly proportional to the amount of secondary structure in the 5′ UTR that must be melted for scanning to occur.
Biosynthesis of many growth-promoting proteins is suppressed on the translation-initiation level, and several forms of cancer exhibit an out-of-balance translation initiation machinery. Although inhibitors of translation exist, most, if not all, act nonspecifically on all translation.